Summary

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing,
or coming back. The use of esomeprazole and aspirin may prevent esophageal cancer in
patients with Barrett's metaplasia. It is not yet known whether esomeprazole is more
effective with or without aspirin in preventing esophageal cancer in patients with Barrett's
metaplasia.

PURPOSE: This randomized phase III trial is studying esomeprazole with or without aspirin to
compare how well they work in preventing esophageal cancer in patients with Barrett's
metaplasia.

Primary Outcomes

Conversion of Barrett's esophagus to adenocarcinoma of the esophagus or high-grade dysplasia

time frame:
assessed every 2 years

Secondary Outcomes

Measure

All causes of mortality

time frame:
assessed annually

Eligibility Criteria

Male or female participants at least 18 years old.

INCLUSION CRITERIA
1. Aged ≥18 years.
2. Circumferential Barrett's metaplasia of at least 1cm in length (≥C1M1) or a tongue of
Barrett's metaplasia of at least 2cm in length (≥C0M2) (irrespective of the presence
now or historically of histologically proven intestinal metaplasia).
3. Able to give written informed consent.
4. WHO performance status of 0 or 1 i.e. fully active and self-caring.
EXCLUSION CRITERIA
1. High grade dysplasia or carcinoma at enrolment.
2. Medical conditions which would make completing endoscopies or completing the trial
difficult including:
1. Frequent transient ischaemic attacks (3 or more) or severe cerebral vascular
accident in the previous 6 months*
2. Severe respiratory disease with arterial oxygen saturation less 90% at rest
3. Severe ischaemic heart disease (exercise tolerance less than 100 yards or life
expectancy < 4 years) or myocardial infarction in the previous 3 months
4. Severe inflammatory bowel disease requiring at least one hospital admission of 5
days in the last year or bowels open > 6 times/day * Patients answering yes to
criterion a. were eligible for the PPI-only (non-aspirin) arms of the trial
3. Continuous/frequent non-steroidal anti-inflammatory drug use or COX-2 inhibitors
(more than 60 days per year in total).
4. Patients with absolute contraindications to PPIs, aspirin or their excipients i.e.
allergies, ulcers, renal impairment or use of oral anticoagulants.
5. Pregnant or lactating women will not undergo endoscopy and may be given dispensation
to stop drug therapy for a year. This should be discussed with the Trial Office.
If a patient was suitable for inclusion but later becomes unsuitable this should be
discussed with the Trial Office before they are withdrawn. Only in exceptional
circumstances should patients not be followed up i.e. withdrawal of consent or current
life threatening disease with poor outcome and therefore unable to tolerate endoscopy. In
these circumstances patients should be followed up in outpatient clinics.

Additional Information

Official title

A Phase III, Randomized, Study of Aspirin and Esomeprazole Chemoprevention in Barrett's Metaplasia

Principal investigator

Janusz Jankowski, MD

Description

PRIMARY OBJECTIVES
- To assess whether intervention with aspirin results in a decreased rate of all causes
of mortality or conversion rate from Barrett's metaplasia to adenocarcinoma or high
grade dysplasia.
- To assess whether high dose PPI (protein pump inhibitor) therapy results in a decreased
rate of all causes of mortality or conversion rate from Barrett's metaplasia to
adenocarcinoma or high grade dysplasia.
SECONDARY OBJECTIVES
- To assess whether intervention with aspirin results in decreased high-grade dysplasia,
in decreased all cause mortality, in decreased oesophageal cancer incidence and in
decreased cause-specific mortality when each is considered separately
- To assess whether intervention with high dose PPI results in decreased high-grade
dysplasia, in decreased all cause mortality, in decreased oesophageal cancer incidence
and in decreased cause-specific mortality when each is considered separately
- To assess whether there are clinical and molecular risk factors which can be identified
in BM (Barrett's Metaplasia) for the development of BA.
- To assess the cost effectiveness of aspirin and/or PPI treatment in the prevention of
BA.
- To assess whether intervention with PPI and/or aspirin induces changes in the
expression of molecular markers for BA.
- To investigate new genes important in the progression of BA, as a unique tissue bank
will be available with a complete endoscopic, histological, physiology and
pharmaceutical history.
- To assess inherited genetic factors for predisposition to oesophagitis above BM, BM,
LGD HGD and BA.
- To assess what the biological risk factors are for cardiac disease and aspirin
resistance.
- To assess gender differences in outcomes.
Cancer Research UK approved the study in 2003 for a 10 year period to run from 1st January
2005 to 31st December 2014. Funding is renewable annually and is dependent on a satisfactory
review by an independent committee.
An application for a funding extension will be made to CRUK 18 months before the end of the
current grant.
A total of 2513 patients have been accrued for this study. They remain on trial medication
and follow up.